Wang Ting, Li Fengjie, Geng Wenwen, Ruan Qingguo, Shi Weiyun
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, People's Republic of China.
Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China.
Cell Death Discov. 2017 May 15;3:17021. doi: 10.1038/cddiscovery.2017.21. eCollection 2017.
Transplant rejection is a major cause of corneal transplantation failure. MicroRNAs (miRNAs) are a family of small RNAs that regulates gene expression in a sequence-specific manner. miRNAs have recently been shown to have important roles in human organ transplantation, but reports of miRNAs directly associated with corneal transplantation rejection remain limited. To investigate the role of miRNAs during corneal allograft rejection, we established a mouse penetrating keratoplasty model and used microarrays to screen for differentially expressed miRNAs. Our results revealed that the expression of miR-122 was significantly decreased in the allogeneic group. Consistent with this result, the expression of cytoplasmic polyadenylation element-binding protein-1 (CPEB1), a direct target of miR-122, was significantly increased. Further analysis demonstrated that miR-122 inhibited inflammatory cytokine-induced apoptosis in corneal keratocytes through the downregulation of its target CPEB1. We also found that increased miR-122 expression significantly reduced the risk of corneal transplantation rejection. Thus, our results indicate that miR-122 is an important miRNA associated with corneal graft rejection and can be used as a therapeutic target for the prevention of immune rejection after keratoplasty.
移植排斥是角膜移植失败的主要原因。微小RNA(miRNA)是一类以序列特异性方式调节基因表达的小RNA。最近研究表明,miRNA在人体器官移植中发挥重要作用,但与角膜移植排斥直接相关的miRNA报道仍然有限。为了研究miRNA在同种异体角膜移植排斥中的作用,我们建立了小鼠穿透性角膜移植模型,并使用微阵列筛选差异表达的miRNA。我们的结果显示,在同种异体组中miR-122的表达显著降低。与此结果一致,miR-122的直接靶标细胞质聚腺苷酸化元件结合蛋白1(CPEB1)的表达显著增加。进一步分析表明,miR-122通过下调其靶标CPEB1抑制炎性细胞因子诱导的角膜基质细胞凋亡。我们还发现,增加miR-122的表达可显著降低角膜移植排斥的风险。因此,我们的结果表明,miR-122是与角膜移植排斥相关的重要miRNA,可作为预防角膜移植术后免疫排斥的治疗靶点。